Project Summary/Abstract Title: Gender identity and own body perception ? implications for the neurobiology of gender dysphoria Individuals with gender dysphoria (GD) experience a stark contrast between their gender identity and their gender assigned at birth. These individuals discover, early in development or later in life, that their body is incongruent with their gender identity. Persistent desire for the physical characteristics and social roles of the other sex contributes to dysphoria. Public awareness of the diversity of gender experience is rising, and issues of those with GD related to self-identity, body image, and medical interventions are becoming more openly discussed across the globe. As this is occurring, more and more individuals are considering, or actually undergoing, treatments to alter their hormones and physical body in attempt to better conform to their gender identity. These interventions, termed medical gender (identity) confirming interventions include gender confirming or sex reassignment surgery and cross sex hormone treatment. Many individuals will obtain these costly, usually irreversible, invasive, and sometimes risky measures to address incongruence between their gender identity and their body. This is quickly becoming a critical global health issue; yet there is very little understanding of what developmental, neurobiological, and sociocultural factors contribute to GD, and who may or may not benefit from these procedures, including those who experience gender ambiguity rather than dysphoria. However, studies of brain structure have found abnormalities in cerebral midline structures, and recent studies found differences in functional connectivity within resting state networks associated with self- referential thinking, as well as differences in the functional neural circuitry related to body perception. The purpose of this study is to address core symptoms of GD?dissatisfaction and estrangement from the own body, and self-referential thinking?by using behavioral experiments and functional and structural neuroimaging to investigate the cerebral networks mediating own body perception in individuals with GD compared to cis- sexual controls, and how they relate to subjective body self-incongruence. We will also investigate the longitudinal effects of estrogen and testosterone treatment on brain functional connections and body phenotype, and how brain structure/function, body phenotype, and hormones pre-treatment may predict who will benefit in terms of improvement of dysphoria and quality of life. As an exploratory aim we will investigate a novel body-morph visual processing task in its reliability and validity for research and clinical use. Studying individuals in both Sweden and the United States will additionally allow us to investigate the effect of stress related to differential cultural stigmatization of non-conforming gender roles. This study will provide valuable information on the neurobiological underpinning of GD and the effects of sex hormones, and promises to uncover functional or structural neural patterns that could predict outcome in terms of body image and quality of life after cross-sex hormone treatment, which ultimately could be used to assist in medical decision-making.